View source for Chitosan

{{Short description|Polysaccharide from crustacean shells}}
{{Use dmy dates|date=January 2025}}
{{Use American English|date=January 2025}}
{{cs1 config|name-list-style=vanc|display-authors=3}}
{{For|the ancient Greek boat called Celox|Celox (boat)}}

{{Chembox
| verifiedrevid  = 441034464
| Name           = Chitosan
| OtherNames     = Poliglusam; Deacetylchitin; Poly-(D)glucosamine; BC; Chitopearl; Chitopharm; Flonac; Kytex
| ImageFile1     = Chitosan_chair.png
| ImageFile2     = Chitosan.jpg
| ImageSize1     = 330px
| ImageName1     = Structure of completely deacetylated chitosan
| Section1       = {{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 64870
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 9012-76-4
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 23R93M6Y64
| InChI1 = 1/C56H103N9O39/c1-87-56(86)65-28-38(84)46(19(10-74)96-55(28)104-45-18(9-73)95-49(27(64)37(45)83)97-39-12(3-67)88-47(85)20(57)31(39)77)103-54-26(63)36(82)44(17(8-72)94-54)102-53-25(62)35(81)43(16(7-71)93-53)101-52-24(61)34(80)42(15(6-70)92-52)100-51-23(60)33(79)41(14(5-69)91-51)99-50-22(59)32(78)40(13(4-68)90-50)98-48-21(58)30(76)29(75)11(2-66)89-48/h11-55,66-85H,2-10,57-64H2,1H3,(H,65,86)/t11-,12-,13-,14-,15-,16-,17-,18-,19-,20-,21-,22-,23-,24-,25-,26-,27-,28-,29-,30-,31-,32-,33-,34-,35-,36-,37-,38-,39-,40-,41-,42-,43-,44-,45-,46-,47-,48+,49+,50+,51+,52+,53+,54+,55+/m1/s1
| InChIKey1 = FLASNYPZGWUPSU-SICDJOISBY
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C56H103N9O39/c1-87-56(86)65-28-38(84)46(19(10-74)96-55(28)104-45-18(9-73)95-49(27(64)37(45)83)97-39-12(3-67)88-47(85)20(57)31(39)77)103-54-26(63)36(82)44(17(8-72)94-54)102-53-25(62)35(81)43(16(7-71)93-53)101-52-24(61)34(80)42(15(6-70)92-52)100-51-23(60)33(79)41(14(5-69)91-51)99-50-22(59)32(78)40(13(4-68)90-50)98-48-21(58)30(76)29(75)11(2-66)89-48/h11-55,66-85H,2-10,57-64H2,1H3,(H,65,86)/t11-,12-,13-,14-,15-,16-,17-,18-,19-,20-,21-,22-,23-,24-,25-,26-,27-,28-,29-,30-,31-,32-,33-,34-,35-,36-,37-,38-,39-,40-,41-,42-,43-,44-,45-,46-,47-,48+,49+,50+,51+,52+,53+,54+,55+/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = FLASNYPZGWUPSU-SICDJOISSA-N
| EINECS =
| SMILES = COC(=O)N[C@@H]1[C@H]([C@@H]([C@H](O[C@H]1O[C@@H]2[C@H](O[C@H]([C@@H]([C@H]2O)N)O[C@@H]3[C@H](O[C@H]([C@@H]([C@H]3O)N)O)CO)CO)CO)O[C@H]4[C@@H]([C@H]([C@@H]([C@H](O4)CO)O[C@H]5[C@@H]([C@H]([C@@H]([C@H](O5)CO)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O[C@H]7[C@@H]([C@H]([C@@H]([C@H](O7)CO)O[C@H]8[C@@H]([C@H]([C@@H]([C@H](O8)CO)O[C@H]9[C@@H]([C@H]([C@@H]([C@H](O9)CO)O)O)N)O)N)O)N)O)N)O)N)O)N)O
| InChI = <!-- 1/C56H103N9O39/c1-87-56(86)65-28-38(84)46(19(10-74)96-55(28)104-45-18(9-73)95-49(27(64)37(45)83)97-39-12(3-67)88-47(85)20(57)31(39)77)103-54-26(63)36(82)44(17(8-72)94-54)102-53-25(62)35(81)43(16(7-71)93-53)101-52-24(61)34(80)42(15(6-70)92-52)100-51-23(60)33(79)41(14(5-69)91-51)99-50-22(59)32(78)40(13(4-68)90-50)98-48-21(58)30(76)29(75)11(2-66)89-48/h11-55,66-85H,2-10,57-64H2,1H3,(H,65,86)/t11-,12-,13-,14-,15-,16-,17-,18-,19-,20-,21-,22-,23-,24-,25-,26-,27-,28-,29-,30-,31-,32-,33-,34-,35-,36-,37-,38-,39-,40-,41-,42-,43-,44-,45-,46-,47-,48+,49+,50+,51+,52+,53+,54+,55+/m1/s1  //-->
  }}
| Section2       = {{Chembox Properties
  }}
| Section8       = {{Chembox Related
| OtherCompounds = [[D-glucosamine|<small>D</small>-glucosamine]] and<br />[[N-Acetylglucosamine|''N''-acetylglucosamine]] (monomers)
  }}
}}

'''Chitosan''' {{IPAc-en|ˈ|k|aɪ|t|ə|s|æ|n}} is a linear [[polysaccharide]] composed of randomly distributed β-(1→4)-linked [[Glucosamine|<small>D</small>-glucosamine]] (deacetylated unit) and [[N-Acetylglucosamine|''N''-acetyl-<small>D</small>-glucosamine]] (acetylated unit). It is made by treating the [[chitin]] shells of shrimp and other crustaceans with an alkaline substance, such as [[sodium hydroxide]].

Chitosan has a number of commercial and possible biomedical uses. It can be used in [[agriculture]] as a seed treatment and [[biopesticide]], helping plants to fight off fungal infections. In [[winemaking]], it can be used as a [[fining agent]], also helping to prevent spoilage. In industry, it can be used in a self-healing [[polyurethane]] [[paint]] coating. In [[medicine]], it is useful in [[bandage]]s to reduce bleeding and as an antibacterial agent; it can also be used to help deliver drugs through the skin.

== History ==
In 1799, British chemist [[Charles Hatchett]] experimented with [[Calcified|decalcifying]] the shells of various crustaceans, finding that a soft, yellow and cartilage-like substance was left behind that we now know to be chitin. In 1859, French physiologist [[Charles Marie Benjamin Rouget]] found that boiling chitin in potassium hydroxide solution could deacetylate it to produce a substance that was soluble in dilute organic acids, that he called ''chitine modifiée''. In 1894, German chemist [[Felix Hoppe-Seyler]] named the substance chitosan. From 1894 to 1930 there was a period of debate and confusion over the exact composition of chitin and particularly whether animal and fungal forms were the same chemicals. In 1930 the first chitosan films and fibres were patented but competition from petroleum-derived polymers limited their uptake. It was not until the 1970s that there was renewed interest in the compound, spurred partly by laws that prevented the dumping of untreated shellfish waste.<ref>{{Cite journal |last=Crini |first=Grégorio |date=December 2019 |title=Historical review on chitin and chitosan biopolymers |url= |journal=Environmental Chemistry Letters |language=en |volume=17 |issue=4 |pages=1623–1643 |doi=10.1007/s10311-019-00901-0 |bibcode=2019EnvCL..17.1623C |issn=1610-3653}}</ref>

==Manufacture ==
[[File:Chitosan Synthese.svg|center|250px|Forming chitosan by partial deacetylation of chitin|alt=]]
[[Image:Pandborealispile.jpg|thumb|250px|right|Commercial chitosan is derived from the shells of shrimp and other sea crustaceans, including ''[[Pandalus borealis]]'', pictured here.<ref>{{cite journal |doi=10.1021/jf00008a032 |title=Isolation and characterization of nutrients and value-added products from snow crab (''Chionoecetes opilio'') and shrimp (''Pandalus borealis'') processing discards |year=1991 |last1=Shahidi |first1=Fereidoon |last2=Synowiecki |first2=Jozef |journal=Journal of Agricultural and Food Chemistry |volume=39 |issue=8 |pages=1527–32 |bibcode=1991JAFC...39.1527S }}</ref>]]

Chitosan is produced commercially by [[acetylation|deacetylation]] of [[chitin]], which is the structural [[wikt:element|element]] in the [[exoskeleton]] of [[crustaceans]] (such as crabs and shrimp) and cell walls of [[fungi]].<ref name=":0" /><ref name=":2">{{Cite journal |last1=Sanjanwala |first1=Dhruv |last2=Londhe |first2=Vaishali |last3=Trivedi |first3=Rashmi |last4=Bonde |first4=Smita |last5=Sawarkar |first5=Sujata |last6=Kale |first6=Vinita |last7=Patravale |first7=Vandana |date=2024-01-01 |title=Polysaccharide-based hydrogels for medical devices, implants and tissue engineering: A review |url=https://www.sciencedirect.com/science/article/pii/S0141813023053874 |journal=International Journal of Biological Macromolecules |volume=256 |issue=Pt 2 |article-number=128488 |doi=10.1016/j.ijbiomac.2023.128488 |pmid=38043653 |issn=0141-8130 |s2cid=265569145|url-access=subscription }}</ref><ref name=":3">{{Cite journal |last1=Kou |first1=Shijie (Gabriel) |last2=Peters |first2=Linda M. |last3=Mucalo |first3=Michael R. |date=2021-02-01 |title=Chitosan: A review of sources and preparation methods |url=https://www.sciencedirect.com/science/article/pii/S0141813020351631 |journal=International Journal of Biological Macromolecules |volume=169 |pages=85–94 |doi=10.1016/j.ijbiomac.2020.12.005 |issn=0141-8130 |pmid=33279563 |s2cid=227522332 |hdl-access=free |hdl=10289/14259|url-access=subscription }}</ref> A common method for obtaining chitosan is the deacetylation of chitin using sodium hydroxide in excess as a reagent and water as a solvent.  The reaction follows [[rate equation|first-order kinetics]] though it occurs in two steps; the [[activation energy]] barrier for the first stage is estimated at 48.8&nbsp;kJ·mol<sup>−1</sup> at {{cvt|25|–|120|C}} and is higher than the barrier to the second stage.<ref>{{Cite journal |last1= Novikov |first1=Vitaly Yu. |last2=Derkach |first2=Svetlana R. |last3=Konovalova |first3=Irina N. |last4=Dolgopyatova |first4=Natalya V. |last5= Kuchina |first5=Yulya A. |display-authors= 3|date=2023-03-30 |title=Mechanism of Heterogeneous Alkaline Deacetylation of Chitin: A Review |journal=Polymers |volume= 15 |issue=7 |page=1729 |doi=10.3390/polym15071729 |issn=2073-4360 |pmid=37050343 |pmc=10097213 |doi-access=free }}</ref><ref>{{Cite journal |last1= Narudin |first1=Nur Alimatul Hakimah |last2=Rosman |first2=Nurul 'Aqilah |last3=Shahrin |first3=Ensan Waatriah ES |last4=Sofyan |first4=Nofrijon |last5= Hanif Mahadi |first5=Abdul |last6=Kusrini |first6=Eny |last7=Hobley |first7=Jonathan |last8=Usman |first8=Anwar |display-authors= 3|date=January 2022 |title=Extraction, characterization, and kinetics of N-deacetylation of chitin obtained from mud crab shells |journal=Polymers and Polymer Composites |language=en |volume=30 |page=096739112211096 |article-number=09673911221109611 |doi=10.1177/09673911221109611 |issn=0967-3911|doi-access=free }}</ref><ref>{{Cite journal |last1=Mohammed |first1=Musarrat H. |last2=Williams |first2= Peter A. |last3=Tverezovskaya |first3=Olga |date=2013-06-01 |title=Extraction of chitin from prawn shells and conversion to low molecular mass chitosan |url=https://www.sciencedirect.com/science/article/pii/S0268005X12002470 |journal=Food Hydrocolloids |volume=31 |issue=2 |pages=166–171 |doi= 10.1016/j.foodhyd.2012.10.021 |issn=0268-005X|url-access=subscription }}</ref>

[[File:Chitosan chemical biological preparation.png|300px|center|Diagrammatic representation of chitosan preparation from natural source in which natural and chemical processing are utilised.]]

The degree of deacetylation (%) can be determined by [[Nuclear magnetic resonance spectroscopy|NMR spectroscopy]] and the degree of deacetylation in commercially available chitosan ranges from 60 to 100%.<ref>{{Cite journal |last1=de Alvarenga |first1=Elson Santiago |last2=Pereira de Oliveira |first2=Cristiane |last3=Roberto Bellato |first3= Carlos |date=2010-05-16 |title=An approach to understanding the deacetylation degree of chitosan |url= https://www.sciencedirect.com/science/article/pii/S0144861710000639 |journal=Carbohydrate Polymers |volume=80 |issue=4 |pages=1155–1160 |doi= 10.1016/j.carbpol.2010.01.037 |issn=0144-8617|url-access=subscription }}</ref><ref>{{Cite journal |last1=Mima |first1=Seiichi |last2=Miya |first2=Masaru |last3=Iwamoto |first3= Reikichi |last4=Yoshikawa |first4=Susumu |date=June 1983 |title=Highly deacetylated chitosan and its properties |url= https://onlinelibrary.wiley.com/doi/10.1002/app.1983.070280607 |journal=Journal of Applied Polymer Science |language=en |volume=28 |issue=6 |pages=1909–1917 |doi=10.1002/app.1983.070280607 |issn=0021-8995|url-access=subscription }}</ref> On average, the molecular weight of commercially produced chitosan is 3800–20,000&nbsp;[[atomic mass unit|daltons]].  

[[Nanocellulose|Nanofibrils]] have been made using chitin and chitosan.<ref>{{cite journal |last1=Jeffryes |first1=C |last2=Agathos |first2=SN| last3= Rorrer |first3=G|title=Biogenic nanomaterials from photosynthetic microorganisms |journal=Current Opinion in Biotechnology|date=June 2015| volume=33 |pages= 23–31|doi=10.1016/j.copbio.2014.10.005|pmid=25445544}}</ref>

===Chemical modifications ===
Chitosan contains the following three functional groups: C2-[[Amine|NH<sub>2</sub>]], C3-[[Hydroxy group|OH]], and C6-OH. C3-OH has a large spatial site resistance and therefore is relatively difficult to [[Chemical modification|modify]]. C2-NH<sub>2</sub> is highly reactive for fine modifications and is the most common modifying group in chitosan.<ref name="Qin 2020">Qin, Y.; Li, P.; Guo, Z. Cationic chitosan derivatives as potential antifungals: A review of structural optimization and applications. Carbohydr. Polym. 2020, 236, 116002.</ref> In chitosan, although [[Amino group|amino groups]] are more prone to [[Nucleophilic substitution|nucleophilic reactions]] than [[Hydroxy group|hydroxyl groups]], both can react non-selectively with [[Electrophilic substitution|electrophilic reagents]] such as acids, chlorides, and [[Haloalkane|haloalkanes]] to [[Functionality (chemistry)#In organic chemistry and material science|functionalize]] them.<ref name="Sahariah 2017">Sahariah, P.; Masson, M. Antimicrobial chitosan and chitosan derivatives: A review of the structure–activity relationship. Biomacromolecules 2017, 18, 3846–3868.</ref> Since chitosan contains a variety of functional groups, it can be functionalized in different ways such as phosphorylation, thiolation, and quaternization to adapt it to specific purposes. 

==== Phosphorylated chitosan ====
Water-soluble phosphorylated chitosan can be obtained by the reaction of [[phosphorus pentoxide]] and chitosan under low-temperature conditions using [[Methanesulfonic acid|methane sulfonic acid]] as the catalyst; phosphorylated chitosan with good antibacterial activity and ionic properties can be prepared by graft copolymerization of chitosan monophosphate.<ref name="Jayakumar 2008">Jayakumar, R.; Selvamurugan, N.; Nair, S.k.V.; Tokura, S.; Tamura, H. Preparative methods of phosphorylated chitin and chitosan—An overview. Int. J. Biol. Macromol. 2008, 43, 221–225.</ref><ref name="Ardean 2021">Ardean, C.; Davidescu, C.M.; Nemeş, N.S.; Negrea, A.; Ciopec, M.; Duteanu, N.; Negrea, P.; Duda-Seiman, D.; Musta, V. Factors influencing the antibacterial activity of chitosan and chitosan modified by functionalization. Int. J. Mol. Sci. 2021, 22, 7449.</ref>  

The good water solubility and [[Chelation|metal chelating properties]] of [[Phosphorylation|phosphorylated]] chitosan and its derivatives make them widely used in [[tissue engineering]], drug delivery carriers, tissue regeneration, and the food industry.<ref name="Liu 2020">Liu, L.; Miao, Y.; Shi, X.; Gao, H.; Wang, Y. Phosphorylated Chitosan Hydrogels Inducing Osteogenic Differentiation of Osteoblasts via JNK and p38 Signaling Pathways. ACS Biomater. Sci. Eng. 2020, 6, 1500–1509.</ref><ref name="Wei 2017">Wei, J.; Xue, W.; Yu, X.; Qiu, X.; Liu, Z. pH Sensitive phosphorylated chitosan hydrogel as vaccine delivery system for intramuscular immunization. J. Biomater. Appl. 2017, 31, 1358–1369.</ref><ref name="Han 2020">Han, G.; Liu, S.; Pan, Z.; Lin, Y.; Ding, S.; Li, L.; Luo, B.; Jiao, Y.; Zhou, C. Sulfonated chitosan and phosphorylated chitosan coated polylactide membrane by polydopamine-assisting for the growth and osteogenic differentiation of MC3T3-E1s. Carbohydr. Polym. 2020, 229, 115517.</ref>  

In tissue engineering, phosphorylated chitosan exhibits improved swelling and ionic conductivity. Although its [[crystallinity]] is reduced, its [[tensile strength]] remains largely unchanged. These properties make it useful for creating scaffolds that can support bone tissue regeneration by binding growth factors and promoting stem cell differentiation into bone-forming cells.<ref name="Muzzarelli 2011">Muzzarelli, R.A. Chitosan composites with inorganics, morphogenetic proteins and stem cells, for bone regeneration. Carbohydr. Polym. 2011, 83, 1433–1445.</ref> Additionally, to enhance the solubility of chitosan-based [[Hydrogel|hydrogels]] at neutral or alkaline pH, the derivative ''N''-methylene phosphonic acid chitosan (NMPC-GLU) has been developed. This material maintains good [[mechanical strength]] and improve [[cell proliferation]], making it valuable for biomedical applications.<ref name="LogithKumar 2016">LogithKumar, R.; KeshavNarayan, A.; Dhivya, S.; Chawla, A.; Saravanan, S.; Selvamurugan, N. A review of chitosan and its derivatives in bone tissue engineering. Carbohydr. Polym. 2016, 151, 172–188.</ref>

==== Thiolated chitosan ====
[[Thiol|Thiolated]] chitosan is produced by attaching thiol groups to the amino groups of chitosan using a thiol-containing [[coupling agent]].<ref name="Bernkop-Schnürch 2004">Bernkop-Schnürch, A.; Hornof, M.; Guggi, D. Thiolated chitosans. Eur. J. Pharm. Biopharm. 2004, 57, 9–17.</ref><ref name="Liu 2021">Liu, X.; Li, X.; Zhang, R.; Wang, L.; Feng, Q. A novel dual microsphere based on water-soluble thiolated chitosan/mesoporous calcium carbonate for controlled dual drug delivery. Mater. Lett. 2021, 285, 129142.</ref> The primary site for this modification is the amino group at the 2nd position of chitosan's glucosamine units. During this process, thioglycolic acid and cysteine mediate the reaction, forming an [[amide bond]] between the thiol group and chitosan. At a pH below 5, thiol activity is reduced, which limits disulfide bond formation.<ref>{{Cite journal |last1=Khan |first1=Ajahar |last2=Alamry |first2=Khalid A. |date=June 2021 |title=Recent advances of emerging green chitosan-based biomaterials with potential biomedical applications: A review |url= |journal=Carbohydrate Research |language=en |volume=506 |article-number=108368 |doi=10.1016/j.carres.2021.108368|pmid=34111686 |doi-access=free }}</ref>

The modified chitosan exhibits improved adhesive properties and stability due to the covalent attachment of the thiol groups. Lower pH reduces oxidation, enhancing its adhesion properties.<ref name="Mueller 2012">Mueller, C.; Verroken, A.; Iqbal, J.; Bernkop-Schnuerch, A. Thiolated chitosans: In vitro comparison of mucoadhesive properties. J. Appl. Polym. Sci. 2012, 124, 5046–5055.</ref><ref name="Laffleur 2017">Laffleur, F. Evaluation of chemical modified hydrogel formulation for topical suitability. Int. J. Biol. Macromol. 2017, 105, 1310–1314.</ref><ref name="Federer 2020">Federer, C.; Kurpiers, M.; Bernkop-Schnurch, A. Thiolated chitosans: A multi-talented class of polymers for various applications. Biomacromolecules 2020, 22, 24–56.</ref> Additionally, thiolated chitosan can interact with cell membrane receptors, improving [[membrane permeability]]<ref name="Zhang 2018">Zhang, Y.; Zhou, S.; Deng, F.; Chen, X.; Wang, X.; Wang, Y.; Zhang, H.; Dai, W.; He, B.; Zhang, Q. The function and mechanism of preactivated thiomers in triggering epithelial tight junctions opening. Eur. J. Pharm. Biopharm. 2018, 133, 188–199.</ref> and showing potential for applications in [[bacterial adhesion prevention]], for example for coating stainless steel.<ref name="Mirani 2018">Mirani, Z.A.; Fatima, A.; Urooj, S.; Aziz, M.; Khan, M.N.; Abbas, T. Relationship of cell surface hydrophobicity with biofilm formation and growth rate: A study on Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. Iran. J. Basic Med. Sci. 2018, 21, 760.</ref><ref name="Xu 2016">Xu, L.Q.; Pranantyo, D.; Neoh, K.-G.; Kang, E.-T.; Fu, G.D. Thiol reactive maleimido-containing tannic acid for the bioinspired surface anchoring and post-functionalization of antifouling coatings. ACS Sustain. Chem. Eng. 2016, 4, 4264–4272.</ref>

==== Ionic chitosan ====
There are two main methods of chitosan quaternization: direct quaternization and indirect quaternization. 

* The direct [[Quaternary amine|quaternization]] of chitosan amino acids treats chitosan with [[Haloalkane|haloalkanes]] under alkaline conditions. Another method is the reaction of chitosan with [[Aldehyde|aldehydes]] first, followed by reduction, and finally with haloalkanes to obtain quaternized chitosan.<ref name="Wei 2019">Wei, L.; Tan, W.; Wang, G.; Li, Q.; Dong, F.; Guo, Z. The antioxidant and antifungal activity of chitosan derivatives bearing Schiff bases and quaternary ammonium salts. Carbohydr. Polym. 2019, 226, 115256.</ref><ref name="Liu 2018">Liu, W.; Qin, Y.; Liu, S.; Xing, R.; Yu, H.; Chen, X.; Li, K.; Li, P. Synthesis, characterization and antifungal efficacy of chitosan derivatives with triple quaternary ammonium groups. Int. J. Biol. Macromol. 2018, 114, 942–949.</ref> 
* The indirect quaternization method refers to introducing small molecules containing quaternary ammonium groups into chitosan, such as glycidyl trimethyl ammonium chloride, (5-bromopentyl) trimethyl ammonium bromide, etc.<ref name="Shagdarova 2019">Shagdarova, B.; Lunkov, A.; Il′ina, A.; Varlamov, V. Investigation of the properties of N-[(2-hydroxy-3-trimethylammonium) propyl] chloride chitosan derivatives. Int. J. Biol. Macromol. 2019, 124, 994–1001.</ref><ref name="De 2016">De Oliveira Pedro, R.; Schmitt, C.C.; Neumann, M.G. Syntheses and characterization of amphiphilic quaternary ammonium chitosan derivatives. Carbohydr. Polym. 2016, 147, 97–103.</ref> Quaternary ammonium groups can further be introduced into the chitosan backbone via [[Azide-alkyne Huisgen cycloaddition|azide-alkyne cycloaddition]],<ref name="Tan 2018">Tan, W.; Zhang, J.; Mi, Y.; Dong, F.; Li, Q.; Guo, Z. Synthesis, characterization, and evaluation of antifungal and antioxidant properties of cationic chitosan derivative via azide-alkyne click reaction. Int. J. Biol. Macromol. 2018, 120, 318–324.</ref> or by dissolving chitosan in alkali and [[urea]] and then reacting it with 3-chloro-2-hydroxypropyl trimethylammonium chloride,<ref name="Song 2018">Song, H.; Wu, H.; Li, S.; Tian, H.; Li, Y.; Wang, J. Homogeneous synthesis of cationic chitosan via new avenue. Molecules 2018, 23, 1921.</ref> which provides a simple and [[Green chemistry|green]] solution to achieve chitosan functionalization.

Cationic derivatives of chitosan have important roles in bioadhesion, absorption enhancement, anti-inflammatory, antibacterial and anti-tumor applications. Chitosan modified with quaternary ammonium groups is one of the most common cationic chitosan derivatives. Quaternized chitosan with a permanent positive charge has increased antimicrobial activity and solubility compared to normal chitosan.<ref name="Mi 2018">Mi, Y.; Tan, W.; Zhang, J.; Wei, L.; Chen, Y.; Li, Q.; Dong, F.; Guo, Z. Synthesis, characterization, and antifungal property of hydroxypropyltrimethyl ammonium chitosan halogenated acetates. Mar. Drugs 2018, 16, 315.</ref>

== Properties ==
Chitosan commonly dissolves via three methods—acidic solutions, ionic liquids, or aqueous CO<sub>2</sub>.<ref>{{Cite web |date=2025-01-09 |title=How to Dissolve Chitosan: Methods and Tips |url=https://www.chemh.com/how-to-dissolve-chitosan-methods-and-tips/ |access-date=2025-04-11 |language=en-US}}</ref> The [[amino]] group in chitosan has a [[pKb|p''K''<sub>b</sub>]] value of ~6.5, which leads to significant protonation in neutral solution, increasing with increased acidity (decreased pH) and the %DA-value. This makes chitosan water-soluble and a bioadhesive which readily binds to negatively charged surfaces<ref>{{cite journal |doi=10.1021/la403124u |pmid=24138057 |author=Dong Woog Lee |title=Strong adhesion and cohesion of chitosan in aqueous solutions |journal=Langmuir |volume=29 |issue=46 |pages=14222–14229 |year=2013|display-authors=etal|pmc=3888206 }}</ref><ref>{{cite journal |doi= 10.1016/j.carbpol.2014.10.033 |pmid=25498713 |author1=Chanoong Lim |author2=Dong Woog Lee |title=Contact time- and pH-dependent adhesion and cohesion of low molecular weight chitosan coated surfaces |journal=Carbohydrate Polymers |volume=117 |issue=6 |pages=887–894 |year=2015|display-authors=etal |doi-access=free }}</ref><ref>{{Cite journal|date=2021-05-01|title=Intermolecular interactions of chitosan: Degree of acetylation and molecular weight| url= https://www.sciencedirect.com/science/article/abs/pii/S0144861721001697|journal=Carbohydrate Polymers| language=en |volume=259 |article-number=117782| doi= 10.1016/j.carbpol.2021.117782|issn=0144-8617|last1=Lim|first1=Chanoong|last2=Hwang|first2=Dong Soo|last3=Lee|first3=Dong Woog| pmid= 33674019| s2cid= 232131640|url-access=subscription}}</ref> such as mucosal membranes. Also, chitosan can effectively bind to other surface via hydrophobic interaction and/or cation-π interaction (chitosan as a cation source) in aqueous solution.<ref>{{Cite journal |last1=Choi |first1=Jieun |last2=Hwang |first2=Dong Soo |last3=Lim |first3=Chanoong |last4=Lee |first4=Dong Woog |date=2024-01-15 |title=Interaction mechanism between low molecular weight chitosan nanofilm and functionalized surfaces in aqueous solutions |url=https://www.sciencedirect.com/science/article/pii/S0144861723009694 |journal=Carbohydrate Polymers |volume=324 |article-number=121504 |doi=10.1016/j.carbpol.2023.121504 |pmid=37985092 |s2cid=264314560 |issn=0144-8617|url-access=subscription }}</ref><ref>{{Cite journal |last1=Kwon |first1=Haeun |last2=Choi |first2=Jieun |last3=Lim |first3=Chanoong |last4=Kim |first4=Junseong |last5=Osman |first5=Asila |last6=Jho |first6=Yongseok |last7=Hwang |first7=Dong Soo |last8=Lee |first8=Dong Woog |date=2025-01-21 |title=Strong Hydrophobic Interaction of High Molecular Weight Chitosan in Aqueous Solution |url=https://pubs.acs.org/doi/10.1021/acs.biomac.4c01333 |journal=Biomacromolecules |volume=26 |issue=2 |pages=1012–1022 |doi=10.1021/acs.biomac.4c01333 |pmid=39836774 |issn=1525-7797|url-access=subscription }}</ref>  The free amine groups on chitosan chains can make [[Cross-link|crosslinked]] polymeric networks with [[dicarboxylic acid]]s to improve chitosan's mechanical properties.<ref name="ReferenceA">{{Cite journal |last1= Moghadas|first1=Babak|last2=Solouk|first2=Atefeh|last3=Sadeghi|first3=Davoud|date=2020-08-24|title=Development of chitosan membrane using non-toxic crosslinkers for potential wound dressing applications|journal=Polymer Bulletin|volume=78|issue=9|pages=4919–4929|language=en|doi=10.1007/s00289-020-03352-8|s2cid=221283821|issn=1436-2449}}</ref> Chitosan enhances the transport of polar [[medication|drugs]] across epithelial surfaces, and is [[Biocompatibility|biocompatible]] and [[biodegradable]]. However, it is not approved by the FDA for drug delivery. Purified quantities of chitosan are available for [[biomedical]] applications.<ref name=":2" /><ref name=":0" />

=== Physicochemical properties ===
Chitosan has biological properties, such as [[Biodegradability of polymers|biodegradability]] and [[biocompatibility]].<ref name="Islam 2017">Islam, S.; Bhuiyan, M.R.; Islam, M. Chitin and chitosan: Structure, properties and applications in biomedical engineering. J. Polym. Environ. 2017, 25, 854–866.</ref> The biological properties of chitosan are closely related to its physicochemical structure, which includes the degree of deacetylation, water content, and molecular weight. Deacetylation refers to the process of removing the acetyl group from chitosan, and this process determines the content of free amine groups in chitosan. Studies have shown that chitosan has good solubility only when the degree of deacetylation is above 85%. The enhanced chitosan uptake is mainly due to the interaction of positively charged chitosan with cell membranes, activation of chlorine–bicarbonate exchange channels, and reorganization of proteins associated with [[Tight junction|epithelial tight junctions]], thus opening epithelial tight junctions.<ref name="Vllasaliu 2012">Vllasaliu, D.; Casettari, L.; Fowler, R.; Exposito-Harris, R.; Garnett, M.; Illum, L.; Stolnik, S. Absorption-promoting effects of chitosan in airway and intestinal cell lines: A comparative study. Int. J. Pharm. 2012, 430, 151–160.</ref>{{better source|date=January 2025}} Chitosan inhibits the growth of different bacteria and fungi by  mechanisms involving several factors, including the degree of deacetylation, pH, divalent cations, and solvent type.{{cn|date=January 2025}}

==Uses==
{{See also|Chitosan nanoparticles}}
===Agricultural and horticultural use===
The agricultural and horticultural uses for chitosan, primarily for plant defense and yield increase,  are based on how this glucosamine polymer influences the biochemistry and molecular biology of the plant cell. The cellular targets are the plasma membrane and nuclear chromatin.  Subsequent changes occur in cell membranes, chromatin, DNA, calcium, [[MAP kinase]], oxidative burst, reactive oxygen species, callose pathogenesis-related (PR) genes, and phytoalexins.<ref>{{cite journal |doi=10.1016/j.plantsci.2013.03.007 |title=Multiple effects of chitosan on plant systems: Solid science or hype |year=2013 |last1=Hadwiger |first1=Lee A. |journal=Plant Science |volume=208 |pages=42–9 |pmid=23683928 |bibcode=2013PlnSc.208...42H }}</ref>

Chitosan was first registered as an active ingredient (licensed for sale) in 1986.<ref>{{cite web | title=Chitosan; Poly-D-glucosamine (128930) Fact Sheet|publisher=Environmental Protection Agency (EPA)|url=https://www3.epa.gov/pesticides/chem_search/reg_actions/registration/fs_PC-128930_01-Jun-03.pdf|date=February 2001}}</ref>

====Natural biocontrol and elicitor====
In [[agriculture]], chitosan is typically used as a natural seed treatment and plant growth enhancer, and as an ecologically friendly [[biopesticide]] substance that boosts the innate ability of plants to defend themselves against fungal infections.<ref>{{cite journal |first1=James C. |last1=Linden |first2=Richard J. |last2=Stoner |first3=Kenneth W. |last3=Knutson |first4=Cecilie A. |last4=Gardner-Hughes |year=2000 |title=Organic disease control elicitors |journal=Agro Food Industry Hi-Tech |volume=11 |issue=5 |pages=32–4}}</ref>

Degraded molecules of chitin/chitosan exist in soil and water. Chitosan applications for plants and crops are regulated in the USA by the [[United States Environmental Protection Agency|Environmental Protection Agency]], and the USDA [[National Organic Program]] regulates its use on organic certified farms and crops.<ref>{{cite web|title=USDA NOP and EPA Rule on Chitosan, ''Federal Register/Vol. 72, No. 236/Monday, December 10, 2007/Rules and Regulation'' |url=http://edocket.access.gpo.gov/2007/pdf/E7-23831.pdf |archive-url=https://web.archive.org/web/20081211232336/http://edocket.access.gpo.gov/2007/pdf/E7-23831.pdf |archive-date=11 December 2008 }}</ref> EPA-approved, biodegradable chitosan products are allowed for use outdoors and indoors on plants and crops grown commercially and by consumers.<ref>{{cite web | title=Chitin and Chitosan Final Registration Review Decision, Document ID: EPA-HQ-OPP-2007-0566-0019|date=  11 December 2008|pages=10–15|work= Regulations.gov |url=http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2007-0566-0019}}</ref>

In the European Union and United Kingdom, chitosan is registered as a "basic substance" for use as a biological [[fungicide]] and [[bactericide]] on a wide range of crops.<ref>{{Cite web| publisher= European Commission| website= ec.europa.eu| date=18 November 2021|title=Expert group for technical advice on organic production. Final report on plant protection (III)|url=https://ec.europa.eu/info/sites/default/files/food-farming-fisheries/farming/documents/final_report_egtop_plant_protection_iii_0.pdf |url-status= live |archive-url= https://web.archive.org/web/20210725071921/https://ec.europa.eu/info/sites/default/files/food-farming-fisheries/farming/documents/final_report_egtop_plant_protection_iii_0.pdf |archive-date=25 July 2021 }}</ref><ref>{{Cite web| title=Basic substances |url=https://ahdb.org.uk/knowledge-library/basic-substances |website=ahdb.org.uk | publisher= Agriculture and Horticulture Development Board |access-date=2021-11-18}}</ref>

The natural biocontrol ability of chitosan should not be confused with the effects of fertilizers or pesticides upon plants or the environment. Chitosan active biopesticides represent a new tier of cost-effective biological control of crops for agriculture and horticulture.<ref name="Goosen1996">{{cite book |first=Mattheus F. A. |last=Goosen|title=Applications of Chitan and Chitosan|url={{google books |plainurl=y |id=3YmDQyVfsDkC|page=132}}|date=1 June 1996 |publisher= CRC Press|isbn=978-1-56676-449-0|pages=132–9}}</ref>  The biocontrol mode of action of chitosan elicits natural innate defense responses within plant to resist insects, pathogens, and soil-borne diseases when applied to foliage or the soil.<ref>{{cite web |last1=Linden |first1=J.C. |last2=Stoner |first2=R.J. |year=2005 |title=Proprietary Elicitor Affects Seed Germination and Delays Fruit Senescence |work=Journal of Food, Agriculture & Environment |url=http://www.yeacrops.com/Elicitor%20-%20Ethylene%20Reduction.pdf}}</ref> Chitosan increases photosynthesis, promotes and enhances plant growth, stimulates nutrient uptake, increases germination and sprouting, and boosts plant vigor.  When used as a seed treatment or seed coating on cotton, corn, seed potatoes, soybeans, sugar beets, tomatoes, wheat, and many other seeds, it elicits an [[innate immunity]] response in developing roots which destroys parasitic cyst nematodes without harming beneficial [[nematodes]] and organisms.<ref>{{cite web| author1= Smiley R.| author2= Cook R.J.| author3= Pauliz T.| title= Seed Treatment for Sample Cereal Grains |publisher= Oregon State University| year= 2002 |url= http://extension.oregonstate.edu/catalog/pdf/em/em8797.pdf#search=%22YEA!%20Seed%20treatment%22 |archive-url= https://web.archive.org/web/20060905104705/http://extension.oregonstate.edu/catalog/pdf/em/em8797.pdf |archive-date=5 September 2006 }}</ref>

Agricultural applications of chitosan can reduce environmental stress due to drought and soil deficiencies, strengthen seed vitality, improve stand quality, increase yields, and reduce fruit decay of  vegetables, fruits and citrus crops <!-- (see photo right}photomissing -->.<ref name=Linden2007>{{cite book |doi=10.1007/978-1-4020-6014-4_65 |chapter=Pre-harvest application of proprietary elicitor delays fruit senescence |title=Advances in Plant Ethylene Research |year=2007 |last1=Linden |first1=J. C. |last2=Stoner |first2=R. J. |isbn=978-1-4020-6013-7 |pages=301–2}}</ref> Horticultural application of chitosan increases blooms and extends the life of cut flowers and Christmas trees. The [[United States Forest Service|US Forest Service]] has conducted research on chitosan to control pathogens in pine trees<ref>{{cite journal |doi=10.1094/MPMI.1997.10.1.135 |title=Defense Response in Slash Pine: Chitosan Treatment Alters the Abundance of Specific mRNAs |year=1997 |last1=Mason |first1=Mary E. |last2=Davis |first2=John M. |journal=Molecular Plant-Microbe Interactions |volume=10 |pages=135–7 |pmid=9002276 |issue=1|bibcode=1997MPMI...10..135M |doi-access=free }}</ref><ref>{{cite journal |last1=Klepzig |first1=Kier D. |last2=Walkinshaw |first2=Charles H. |year=2003 |title=Cellular response of loblolly pine to wound inoculation with bark beetle-associated fungi and chitosan | publisher=Res. Pap. SRS-30. Asheville, NC; US Department of Agriculture, [[United States Forest Service|Forest Service]], Southern Research Station. 9P |volume=030 |website= treesearch.fs.fed.us| url=http://www.treesearch.fs.fed.us/pubs/5322}}</ref> and increase resin pitch outflow which resists pine beetle infestation.<ref>{{cite news|url= http://www.publicbroadcasting.net/kunc/news.newsmain/article/1/0/1552856/Regional/Solution.for.Pine.Bark.Beetles.May.Help.Front.Range.Trees|publisher= KUNC 91.5 FM, NPR |work= Morning Edition |location= Greeley, Colorado |title=Solution for Pine Bark Beetles May Help Front Range Trees |last= O'Toole| first= Erin |date= 10 September 2009|access-date=25 October 2009|archive-date=24 September 2009|archive-url= https://web.archive.org/web/20090924030202/http://www.publicbroadcasting.net/kunc/news.newsmain/article/1/0/1552856/Regional/Solution.for.Pine.Bark.Beetles.May.Help.Front.Range.Trees}}</ref>

Chitosan has been studied for applications in agriculture and horticulture dating back to the 1980s.<ref>{{cite journal |doi= 10.1104/pp.85.4.1123 |title=Biochemistry of Oleoresinosis: Monoterpene and Diterpene Biosynthesis in Lodgepole Pine Saplings Infected with Ceratocystis clavigera or Treated with Carbohydrate Elicitors |year=1987 |last1=Croteau |first1=R. |last2=Gurkewitz |first2=S. |last3=Johnson |first3=M. A. |last4=Fisk |first4=H. J. |journal=Plant Physiology |volume= 85 |issue=4 |pages=1123–8 |pmid=16665815 |pmc=1054405}}</ref> By 1989, chitosan salt solutions were applied to crops for improved freeze protection or to crop seed for seed priming.<ref>{{cite web | title=Treatment of Plants with Chitosan Salts, 1989, Patent WO/1989/007395 | url= https://patentscope.wipo.int/search/en/detail.jsf?docId=WO1989007395 | website= Patentscope| publisher= WIPO }}</ref> Shortly thereafter, chitosan salt received the first ever [[biopesticide]] label from the EPA, then followed by other [[intellectual property]] applications.

Chitosan has been used to protect plants in space, as well, exemplified by [[NASA]]'s experiment to protect adzuki beans grown aboard the space shuttle and [[Mir]] space station in 1997.<ref>{{cite web|author=Stoner, R.|title=Progressive Plant Growing Has Business Blooming, Environmental and Agricultural Resources|work=NASA.gov |year=2006|pages=68–71|url=http://www.nasa.gov/vision/earth/technologies/aeroponic_plants.html|access-date=17 April 2009|archive-date=21 December 2015|archive-url= https://web.archive.org/web/20151221075502/http://www.nasa.gov/vision/earth/technologies/aeroponic_plants.html}}.</ref> NASA results revealed chitosan induces increased growth (biomass) and pathogen resistance due to elevated levels of β-(1→3)-glucanase enzymes within plant cells. NASA confirmed chitosan elicits the same effect in plants on earth.<ref>{{cite web |last1=Linden |first1=James C. |last2=Stoner |first2=Richard J. |title=YEA! Elicitor Response Comparison to Chitin / Chitosan in Mung Bean and Adzuki Bean Germination Experiments |date=21 October 2008 |url=http://www.agrihouse.com/references/compare.pdf}}</ref>

In 2008, the EPA approved natural broad-spectrum elicitor status for an ultralow molecular active ingredient of 0.25% chitosan.<ref>{{cite journal | title= Chitin/Chitosan, Farnesol/Nerolidol and Nosema locustae Final Registration Review Decision|journal= Federal Register Notice of Availability |date=24 December 2008 |volume =73|issue=248|url=http://www.epa.gov/EPA-PEST/2008/December/Day-24/p30496.htm|archive-url=https://archive.today/20120729201111/http://www.epa.gov/EPA-PEST/2008/December/Day-24/p30496.htm|archive-date=29 July 2012}}</ref> A natural chitosan elicitor solution for agriculture and horticultural uses was granted an amended label for foliar and irrigation applications by the EPA in 2009.<ref name=Linden2007/> Given its low potential for toxicity and abundance in the natural environment, chitosan does not harm people, pets, wildlife, or the environment when used according to label directions.<ref>{{cite web | title= Chitosan Exemption from the Requirement of a Tolerance |url=http://www.epa.gov/fedrgstr/EPA-PEST/1995/April/Day-19/pr-224.html|archive-url=https://web.archive.org/web/20030120110109/http://www.epa.gov/fedrgstr/EPA-PEST/1995/April/Day-19/pr-224.html|archive-date=20 January 2003| publisher=US Environmental Protection Agency |website= epa.gov}}</ref><ref>{{cite web|title=Control Strategies to reduce postharvest decay of fresh fruits and vegetables|url=http://pubsearch.arsnet.usda.gov/search?q=chitosan&requiredfields=spsite_id%3A12750000%7Cspsite_id%3A12-50-00-00&btnG=Go%21&filter=0&as_sitesearch=ars.usda.gov&ie=&output=xml_no_dtd&client=ars_frontend&proxystylesheet=ars_frontend&lr=&oe=|archive-url=https://archive.today/20120716140043/http://pubsearch.arsnet.usda.gov/search?q=chitosan&requiredfields=spsite_id:12750000%7Cspsite_id:12-50-00-00&btnG=Go!&filter=0&as_sitesearch=ars.usda.gov&ie=&output=xml_no_dtd&client=ars_frontend&proxystylesheet=ars_frontend&lr=&oe=|archive-date=2012-07-16|work=USDA.gov}}</ref><ref>{{cite web | title=Chitosan; Poly-D-glucosamine (128930) Fact Sheet |date=2 May 2006 | publisher=US Environmental Protection Agency |url=http://www.epa.gov/pesticides/biopesticides/ingredients/factsheets/factsheet_128930.htm |archive-url=https://web.archive.org/web/20030211043004/http://www.epa.gov/pesticides/biopesticides/ingredients/factsheets/factsheet_128930.htm |archive-date=11 February 2003 |website= epa.gov| access-date=10 July 2006}}</ref> Chitosan blends do not work against [[bark beetle]]s when put on a tree's leaves or in its soil.<ref>{{Cite journal| last1= Klepzig |first1=Kier D|last2=Strom|first2=Brian L|date=2010-08-20|title=Effects of a commercial chitosan formulation on bark beetle (Coleoptera: Curculionidae) resistance parameters in loblolly pine|url=https://www.srs.fs.fed.us/pubs/ja/2011/ja_2011_klepzig_002.pdf |journal=Journal of Entomological Science| publication-date=2011-04-01|volume=46|issue=2|pages=124–134|doi=10.18474/0749-8004-46.2.124|s2cid=12241255|access-date=2021-03-06|quote=. . . application of a commercially-prepared chitosan formulation to loblolly pine produced inconsistent responses in tree parameters associated with bark beetle resistance, suggesting that exogenously applied chitosan preparations have limited utility for managing bark beetles.|via=USDA Forest Service Southern Research Station}}</ref>

===Filtration===
Chitosan can be used in [[hydrology]] as a part of a [[filtration]] process.<ref name="yong">{{cite book|pmid=25367132|year=2015|last1=Yong|first1=S. K|volume=233|pages=1–43|last2=Shrivastava|first2=M|last3=Srivastava|first3=P|last4=Kunhikrishnan|first4=A|last5=Bolan|first5=N |title=Reviews of Environmental Contamination and Toxicology Volume 233 |chapter=Environmental Applications of Chitosan and Its Derivatives |journal=Reviews of Environmental Contamination and Toxicology |doi=10.1007/978-3-319-10479-9_1|isbn=978-3-319-10478-2}}</ref> Chitosan causes the fine sediment particles to bind together, and is subsequently removed with the sediment during sand filtration. It also removes [[heavy mineral]]s, [[dye]]s, and oils from the water.<ref name=yong/> As an additive in water filtration, chitosan combined with sand filtration removes up to 99% of  [[turbidity]].<ref>{{cite web | author = Alan Woodmansey | title=Chitosan Treatment of Sediment Laden Water – Washington State I-90 Issaquah Project | url=https://www.fhwa.dot.gov/engineering/geotech/ | date=19 March 2002 | work = Federal Highway Administration | publisher=U.S. Department of Transportation | access-date=10 July 2006}}</ref> Chitosan is among the biological adsorbents used for heavy metals removal without negative environmental impacts.<ref name=yong/>

In combination with [[bentonite]], [[gelatin]], [[silica gel]], [[isinglass]], or other [[fining agents (wine)|fining agents]], it is used to [[clarify (wine)|clarify]] [[wine]], [[mead]], and [[beer]]. Added late in the brewing process, chitosan improves [[flocculation]], and removes yeast cells, fruit particles, and other detritus that cause hazy wine.<ref>{{cite web  | url=http://www.makewine.com/makewine/fining.html  | title=Fining and Clarifying Agents  | first=Terry  | last=Rayner  | access-date=18 July 2006 | archive-url = https://web.archive.org/web/20060616062535/http://makewine.com/makewine/fining.html| archive-date = 16 June 2006}}</ref>

===Winemaking and fungal source chitosan===
Chitosan has a long history for use as a [[fining (wine)|fining]] agent in winemaking.<ref>{{cite web|url=https://winemakermag.com/26-a-clearer-understanding-of-fining-agents|title=A clearer understanding of fining agents|author=Chorniak J|publisher=Wine Maker Magazine|date=October 2007|access-date=24 May 2014}}</ref><ref>{{Cite journal | pmid = 22545592| year = 2012| last1 = Quintela| first1 = S| title = Ochratoxin a removal from red wine by several oenological fining agents: Bentonite, egg albumin, allergen-free adsorbents, chitin and chitosan| journal = Food Additives & Contaminants: Part A| volume = 29| issue = 7| pages = 1168–74| last2 = Villarán| first2 = M. C.| last3 = López De Armentia| first3 = I| last4 = Elejalde| first4 = E| doi = 10.1080/19440049.2012.682166| s2cid = 8215176}}</ref> Fungal source chitosan has shown an increase in settling activity, reduction of oxidized polyphenolics in juice and wine, chelation and removal of copper (post-racking) and control of the spoilage [[yeast (wine)|yeast]] ''[[Brettanomyces]]''.{{citation needed|date=October 2021}} These products and uses are approved for European use by the EU and [[Office International de la Vigne et du Vin|OIV]] standards.<ref>{{cite journal |doi=10.1007/s10295-004-0112-2 |title=Selective antimicrobial action of chitosan against spoilage yeasts in mixed culture fermentations |year=2004 |last1=Escudero-Abarca |first1=Blanca I. |last2=Escudero-Abarca |first2=M. Guadalupe |last3=Aguilar-Uscanga |first3=Patricia M. |last4=Hayward-Jones |first4=Patricia |last5=Mendoza |first5=Mario |last6=Ramírez |first6=Leticia |journal=Journal of Industrial Microbiology and Biotechnology |volume=31 |pages=16–22 |pmid=14747932 |issue=1|s2cid=250412 |doi-access=free }}</ref>{{Failed verification|date=October 2021|reason=Source specifies using chitosan from crustatceans.  Source does not mention OIV nor the EU.}}

===Wound management===
Chitosan-based wound dressings have been widely explored for a variety of acute and chronic wounds. Chitosan has the ability to adhere to [[fibrinogen]], which produces increased [[platelet]] adhesion, causing clotting of blood and hemostasis.<ref name=":0">{{Cite journal |last1=Sanjanwala |first1=Dhruv |last2=Londhe |first2=Vaishali |last3=Trivedi |first3=Rashmi |last4=Bonde |first4=Smita |last5=Sawarkar |first5=Sujata |last6=Kale |first6=Vinita |last7=Patravale |first7=Vandana |date=2022-11-28 |title=Polysaccharide-based hydrogels for drug delivery and wound management: A review |url=https://www.tandfonline.com/doi/full/10.1080/17425247.2022.2152791 |journal=Expert Opinion on Drug Delivery |volume=19 |issue=12 |language=en |pages=1664–1695 |doi=10.1080/17425247.2022.2152791 |pmid=36440488 |s2cid=254041961 |issn=1742-5247|url-access=subscription }}</ref><ref>{{Cite journal |last1=Ullah |first1=Faheem |last2=Othman |first2=Muhammad Bisyrul Hafi |last3=Javed |first3=Fatima |last4=Ahmad |first4=Zulkifli |last5=Akil |first5=Hazizan Md. |date=2015-12-01 |title=Classification, processing and application of hydrogels: A review |url=https://www.sciencedirect.com/science/article/pii/S0928493115302393 |journal=Materials Science and Engineering: C |language=en |volume=57 |pages=414–433 |doi=10.1016/j.msec.2015.07.053 |pmid=26354282 |issn=0928-4931|url-access=subscription }}</ref><ref name=":1">{{Cite journal |last1=Feng |first1=Peipei |last2=Luo |first2=Yang |last3=Ke |first3=Chunhai |last4=Qiu |first4=Haofeng |last5=Wang |first5=Wei |last6=Zhu |first6=Yabin |last7=Hou |first7=Ruixia |last8=Xu |first8=Long |last9=Wu |first9=Songze |date=2021 |title=Chitosan-Based Functional Materials for Skin Wound Repair: Mechanisms and Applications |journal=Frontiers in Bioengineering and Biotechnology |volume=9 |article-number=650598 |doi=10.3389/fbioe.2021.650598 |pmid=33681176 |pmc=7931995 |issn=2296-4185|doi-access=free }}</ref> Chitosan [[Antihemorrhagic|hemostatic agents]] are salts made from mixing chitosan with an organic acid (such as succinic or lactic acid).<ref name="How Chitosan Works">{{cite journal |last1=Baldrick |first1=Paul |year=2010 |title=The safety of chitosan as a pharmaceutical excipient |journal=Regulatory Toxicology and Pharmacology |volume=56 |issue=3 |pages=290–9 |doi=10.1016/j.yrtph.2009.09.015 |pmid=19788905}}</ref><ref>{{Cite journal |last1=Guo |first1=Baolin |last2=Dong |first2=Ruonan |last3=Liang |first3=Yongping |last4=Li |first4=Meng |date=2021-11-01 |title=Haemostatic materials for wound healing applications |url=https://www.nature.com/articles/s41570-021-00323-z |journal=Nature Reviews Chemistry |language=en |volume=5 |issue=11 |pages=773–791 |doi=10.1038/s41570-021-00323-z |pmid=37117664 |s2cid=237551413 |issn=2397-3358|url-access=subscription }}</ref> Chitosan may have other properties conducive to wound healing, including antibacterial and antifungal activity, which remain under preliminary research.<ref name=":0" /><ref name="Duc2011">{{cite book |url=https://books.google.com/books?id=oa8YpRsD1kkC&pg=RA1-PA229 |title=Comprehensive Biomaterials |date=2011 |publisher=Elsevier |isbn=978-0-08-055294-1 |editor1-last=Ducheyne |editor1-first=Paul |location=Amsterdam |page=229 |editor2-last=Healy |editor2-first=Kevin |editor3-last=Hutmacher |editor3-first=Dietmar E. |editor4-last=Grainger |editor4-first=David W. |editor5-last=Kirkpatrick |editor5-first=C. James}}</ref> 

Chitosan is used within some wound dressings to decrease bleeding.<ref name="Zh2015" /> Upon contact with blood, the bandage becomes sticky, effectively sealing the laceration.<ref name="pmid28799228">{{cite journal |vauthors=Singh R, Shitiz K, Singh A|date=December 2017 |title=Chitin and chitosan: biopolymers for wound management|journal=International Wound Journal |volume=14 |issue=6 |pages=1276–1289 |doi=10.1111/iwj.12797|pmid=28799228|pmc=7949833}}</ref>  Chitosan hydrogel-based wound dressings have also been found useful as burn dressings, and for the treatment of chronic diabetic wounds and hydrofluoric acid burns.<ref name=":0" /><ref name="Zh2015" />

Chitosan-containing wound dressings received approval for medical use in the United States in 2003.<ref name="Zh2015">{{cite journal|last1=Zhang|first1=Yin-Juan|last2=Gao|first2=Bo|last3=Liu|first3=Xi-Wen|title=Topical and effective hemostatic medicines in the battlefield|journal=Int J Clin Exp Med|year=2015|volume=8|issue=1|pages=10–19|pmid=25784969|pmc=4358424}}</ref>

===Temperature-sensitive hydrogels===
Chitosan is dissolved in dilute organic acid solutions but is insoluble in high concentrations of hydrogen ions at pH 6.5 and is precipitated as a gel-like compound.<ref name=rahm/> Chitosan is positively charged by amine groups, making it suitable for binding to negatively charged molecules. However, it has disadvantages such as low mechanical strength and low-temperature response rate; it must be combined with other gelling agents to improve its properties.<ref name=rahm/> Using glycerolphosphate salts (possessing a single anionic head) without chemical modification or cross-linking, the pH-dependent gelation properties can be converted to temperature-sensitive gelation properties. In the year 2000, Chenite was the first to design the temperature-sensitive chitosan hydrogels drug delivery system using chitosan and β-glycerol phosphate. This new system can remain in the liquid state at room temperature, while becoming gel with increasing temperature above the physiological temperature (37&nbsp;°C). Phosphate salts cause a particular behaviour in chitosan solutions, thereby allowing these solutions to remain soluble in the physiological pH range (pH&nbsp;7), and they will be gel only at body temperature. When the liquid solution of chitosan-glycerol phosphate, containing the drug, enters the body through a syringe injection, it becomes a water-insoluble gel at 37&nbsp;°C. The entrapped drug particles between the hydrogel chains will be gradually released.<ref name="rahm">{{cite journal |doi=10.1155/2021/6640893 |title=Thermosensitive Chitosan-β-Glycerophosphate Hydrogels as Targeted Drug Delivery Systems: An Overview on Preparation and Their Applications |year=2021 |journal=Advances in Pharmacological and Pharmaceutical Sciences |volume=2021 |page=17 |pmid=34036263|pmc=8116164 |doi-access=free |last1=Rahmanian-Devin |first1=Pouria |last2=Baradaran Rahimi |first2=Vafa |last3=Askari |first3=Vahid Reza }}</ref>

===Research===
Chitosan and derivatives have been developed for their potential use in [[nanomaterial]]s, [[bioadhesive]]s, [[Dressing (medical)|wound dressing materials]],<ref name=":0" /><ref name="ReferenceA"/> [[drug delivery]] systems, [[enteric coating]]s, and in [[medical device]]s.<ref name=":0" /><ref name=":2" /><ref>{{cite journal |last1=Federer |first1=C |last2=Kurpiers |first2=M |last3=Bernkop-Schnürch |first3=A |title=Thiolated Chitosans: A Multi-talented Class of Polymers for Various Applications |journal=Biomacromolecules |date=2021 |volume=22 |issue=1 |pages=24–56 |doi=10.1021/acs.biomac.0c00663 |pmid=32567846|pmc=7805012 }}</ref> For example, chitosan nanoparticles produced using sodium tripolyphosphate as crosslinker are stable and biocompatible enough to be used as drug delivery materials.<ref>{{Cite journal |last1=Haider |first1=Ammar |last2=Khan |first2=Shabana |last3=Iqbal |first3=Dure Najaf |last4=Shrahili |first4=Mansour |last5=Haider |first5=Sajjad |last6=Mohammad |first6=Khaled |last7=Mohammad |first7=Abdulrahman |last8=Rizwan |first8=Muhammad |last9=Kanwal |first9=Qudsia |last10=Mustafa |first10=Ghulam |date=April 2024 |title=Advances in chitosan-based drug delivery systems: A comprehensive review for therapeutic applications |url=https://linkinghub.elsevier.com/retrieve/pii/S0014305724002441 |journal=European Polymer Journal |language=en |volume=210 |article-number=112983 |doi=10.1016/j.eurpolymj.2024.112983|bibcode=2024EurPJ.21012983H |url-access=subscription }}</ref>

===Bioprinting===
[[Image:Objects made of chitosan.png|thumb|Objects made from chitosan<ref name=MME/>]]

[[Bioinspiration|Bioinspired]] [[biomimetics#Bio-inspired technologies|materials]], a manufacturing concept inspired by natural [[nacre]], [[shrimp]] [[carapace]], or insect [[cuticle]]s,<ref>{{Cite journal | pmid = 14566805| year = 2003| last1 = Tampieri| first1 = A| title = Biologically inspired synthesis of bone-like composite: Self-assembled collagen fibers/hydroxyapatite nanocrystals| journal = Journal of Biomedical Materials Research| volume = 67| issue = 2| pages = 618–25| last2 = Celotti| first2 = G| last3 = Landi| first3 = E| last4 = Sandri| first4 = M| last5 = Roveri| first5 = N| last6 = Falini| first6 = G| doi = 10.1002/jbm.a.10039}}</ref><ref>{{Cite journal | pmid = 15696277| year = 2005| last1 = Tampieri| first1 = A| title = From biomimetic apatites to biologically inspired composites| journal = Analytical and Bioanalytical Chemistry| volume = 381| issue = 3| pages = 568–76| last2 = Celotti| first2 = G| last3 = Landi| first3 = E| doi = 10.1007/s00216-004-2943-0| s2cid = 25745619}}</ref><ref>{{Cite journal | pmid = 24635413| year = 2014| last1 = Cheng| first1 = Q| title = Bioinspired layered materials with superior mechanical performance| journal = Accounts of Chemical Research| volume = 47| issue = 4| pages = 1256–66| last2 = Jiang| first2 = L| last3 = Tang| first3 = Z| doi = 10.1021/ar400279t}}</ref> has led to development of [[3D bioprinting|bioprinting]] methods to manufacture large scale consumer objects using chitosan.<ref>{{Cite journal | pmid = 18596653| pmc = 6245338| year = 2008| last1 = Tajik| first1 = H| title = Preparation of chitosan from brine shrimp (Artemia urmiana) cyst shells and effects of different chemical processing sequences on the physicochemical and functional properties of the product| journal = Molecules | volume = 13| issue = 6| pages = 1263–74| last2 = Moradi| first2 = M| last3 = Rohani| first3 = S. M.| last4 = Erfani| first4 = A. M.| last5 = Jalali| first5 = F. S.| doi=10.3390/molecules13061263| doi-access = free}}</ref><ref>{{Cite journal | pmid = 22162193| year = 2012| last1 = Fernandez| first1 = J. G.| title = Unexpected strength and toughness in chitosan-fibroin laminates inspired by insect cuticle| journal = Advanced Materials| volume = 24| issue = 4| pages = 480–4| last2 = Ingber| first2 = D. E.| doi = 10.1002/adma.201104051| bibcode = 2012AdM....24..480F| s2cid = 205243157}}</ref> This method is based on replicating the molecular arrangement of chitosan from natural materials into fabrication methods, such as [[injection molding]] or [[molding (process)|mold casting]].<ref>{{cite web|title=Promising solution to plastic pollution|url=http://news.harvard.edu/gazette/story/2014/05/promising-solution-to-plastic-pollution/|author=Wyss Institute Communications|date=May 2014|publisher=Harvard Gazette, Harvard University, Boston, MA |access-date=23 May 2014}}</ref> Once discarded, chitosan-constructed objects are [[biodegradable]] and non-[[toxic]].<ref>{{Cite journal | pmid = 23608103| year = 2013| last1 = Shukla| first1 = S. K.| title = Chitosan-based nanomaterials: A state-of-the-art review| journal = International Journal of Biological Macromolecules| volume = 59| pages = 46–58| last2 = Mishra| first2 = A. K.| last3 = Arotiba| first3 = O. A.| last4 = Mamba| first4 = B. B.| doi = 10.1016/j.ijbiomac.2013.04.043}}</ref> The method is used to engineer and bioprint human [[organ (anatomy)|organs]] or [[tissue (biology)|tissues]].<ref>{{Cite journal | doi = 10.1088/1758-5082/5/4/045003| pmid = 24060622| title = Customized biomimetic scaffolds created by indirect three-dimensional printing for tissue engineering| journal = Biofabrication| volume = 5| issue = 4| article-number = 045003| year = 2013| last1 = Lee | first1 = J. Y. | last2 = Choi | first2 = B. | last3 = Wu | first3 = B. | last4 = Lee | first4 = M. | pmc = 3852984| bibcode = 2013BioFa...5d5003L}}</ref><ref>{{cite web|url=http://www.industryweek.com/around-web/manufacturing-3-d-objects-just-got-easier-new-bioplastic|author=Selko A|publisher=Industry Week|title=Manufacturing 3-D objects just got easier with new bioplastic|date=6 March 2014|access-date=24 May 2014}}</ref>

[[Pigment]]ed chitosan objects can be recycled,<ref name="ingber">{{Cite journal | doi = 10.1002/mame.201300426| title = Manufacturing of Large-Scale Functional Objects Using Biodegradable Chitosan Bioplastic| journal = Macromolecular Materials and Engineering| pages = 932–938| year = 2014| last1 = Fernandez | first1 = J. G. | last2 = Ingber | first2 = D. E. | volume=299| issue = 8}}</ref> with the option of reintroducing or discarding the dye at each recycling step, enabling reuse of the polymer independently of colorants.<ref>{{cite web|title=Manufacturing a solution to planet-clogging plastics |url=http://wyss.harvard.edu/viewpressrelease/144/manufacturing-a-solution-to-planetclogging-plastics-|date=3 March 2014|access-date=5 June 2014|publisher=Hansjorg Wyss Institute for Biologically Inspired Engineering, Harvard University}}</ref><ref>{{Cite journal | pmid = 22302077| year = 2012| last1 = Zhao| first1 = Y| title = Bio-inspired variable structural color materials| journal = Chemical Society Reviews| volume = 41| issue = 8| pages = 3297–317| last2 = Xie| first2 = Z| last3 = Gu| first3 = H| last4 = Zhu| first4 = C| last5 = Gu| first5 = Z| doi = 10.1039/c2cs15267c}}</ref> Unlike other plant-based [[bioplastic]]s (e.g. [[cellulose]], [[starch]]), the main natural sources of chitosan come from marine environments and do not compete for land or other human resources.<ref name="MME">{{cite journal|vauthors=Fernandez J, Ingber D |title=Manufacturing of large-scale functional objects using biodegradable chitosan bioplastic|journal=Macromolecular Materials and Engineering|date=February 2014|doi=10.1002/mame.201300426|volume=299|issue=8|pages=932–938}}</ref><ref>{{cite web|title=Chitosan bioplastic|url=http://wyss.harvard.edu/viewpage/531|publisher=Wyss Institute Communications, Hansjorg Wyss Institute for Biologically Inspired Engineering, Harvard University|date=2014|access-date=24 May 2014|archive-url=https://web.archive.org/web/20140524022833/http://wyss.harvard.edu/viewpage/531|archive-date=24 May 2014}}</ref>

[[3D bioprinting]] of [[tissue engineering]] scaffolds for creating artificial tissues and organs is another application where chitosan has gained popularity. Chitosan has high [[biocompatibility]], [[Biodegradation|biodegradability]], and [[antimicrobial]], [[Hemostasis|hemostatic]], [[wound healing]] and immunomodulatory activities which make it suitable for making artificial tissues.<ref name=":2" /><ref>{{Cite journal |last1=Croisier |first1=Florence |last2=Jérôme |first2=Christine |date=2013-04-01 |title=Chitosan-based biomaterials for tissue engineering |journal=European Polymer Journal |series=Biobased Polymers and Related Materials |volume=49 |issue=4 |pages=780–792 |doi=10.1016/j.eurpolymj.2012.12.009 |bibcode=2013EurPJ..49..780C |issn=0014-3057|doi-access=free }}</ref><ref>{{Cite journal |last1=Kim |first1=In-Yong |last2=Seo |first2=Seog-Jin |last3=Moon |first3=Hyun-Seuk |last4=Yoo |first4=Mi-Kyong |last5=Park |first5=In-Young |last6=Kim |first6=Bom-Chol |last7=Cho |first7=Chong-Su |date=2008-01-01 |title=Chitosan and its derivatives for tissue engineering applications |url=https://www.sciencedirect.com/science/article/pii/S0734975007000948 |journal=Biotechnology Advances |volume=26 |issue=1 |pages=1–21 |doi=10.1016/j.biotechadv.2007.07.009 |pmid=17884325 |issn=0734-9750|url-access=subscription }}</ref>

=== Weight loss ===
Chitosan is marketed in a tablet form as a "fat binder".<ref>{{cite book|author1=Allison Sarubin-Fragakis, Cynthia Thomson|title=The Health Professional's Guide to Popular Dietary Supplements|date=2007|publisher=Academy of Nutrition and Dietetics|page=96|url=https://books.google.com/books?id=KA8vU6XKfIAC&pg=PA96|isbn=978-0-88091-363-8}}</ref> Although the effect of chitosan on lowering [[cholesterol]] and body weight has been evaluated, the effect appears to have no or low clinical importance.<ref name=Rios2016>{{cite journal |last1=Ríos-Hoyo |first1=A |last2=Gutiérrez-Salmeán |first2=G |title=New Dietary Supplements for Obesity: What We Currently Know. |journal=Current Obesity Reports |date=June 2016 |volume=5 |issue=2 |pages=262–70 |doi=10.1007/s13679-016-0214-y |pmid=27053066|s2cid=12071766 }}</ref><ref name="drugs">{{cite web |title=Chitosan |url=https://www.drugs.com/npp/chitosan.html |publisher=Drugs.com |access-date=4 November 2018 |date=12 February 2018}}</ref> Reviews from 2016 and 2008 found there was no significant effect, and no justification for overweight people to use chitosan supplements.<ref name=Rios2016/><ref name="cochrane">{{cite journal |doi=10.1002/14651858.CD003892.pub3 |title=Chitosan for overweight or obesity |journal=Cochrane Database of Systematic Reviews |year=2008 |last1=Jull |first1=Andrew B |last2=Ni Mhurchu |first2=Cliona |last3=Bennett |first3=Derrick A |last4=Dunshea-Mooij |first4=Christel AE |last5=Rodgers |first5=Anthony |editor1-last=Jull |editor1-first=Andrew B |pmid=18646097 |issue=3 |article-number=CD003892}}</ref> In 2015, the U.S. [[Food and Drug Administration]] issued a public advisory about supplement retailers who made exaggerated claims concerning the supposed weight loss benefit of various products.<ref>{{cite web |publisher=US Food and Drug Administration| title=Beware of Products Promising Miracle Weight Loss|url=https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm246742.htm|archive-url=https://web.archive.org/web/20110316224354/http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm246742.htm|archive-date=16 March 2011|date=5 January 2015|access-date=4 November 2018}}</ref>

=== Biodegradable antimicrobial food packaging ===
Microbial contamination of food products accelerates the deterioration process and increases the risk of foodborne illness caused by potentially life-threatening pathogens.<ref name="altay">{{cite journal | last1=Al-Tayyar | first1=Nasser A. | last2=Youssef | first2=Ahmed M. | last3=Al-hindi | first3=Rashad | title=Antimicrobial food packaging based on sustainable Bio-based materials for reducing foodborne pathogens: A review | journal=Food Chemistry| volume=310 | year=2020 | issn=0308-8146 | doi=10.1016/j.foodchem.2019.125915 | article-number=125915|pmid=31841936| doi-access=free }}</ref> Ordinarily, food contamination originates superficially, requiring surface treatment and packaging as crucial factors to assure food quality and safety.<ref name=altay/> Biodegradable chitosan films have potential for preserving various food products, retaining their firmness and restricting weight loss due to dehydration. In addition, composite biodegradable films containing chitosan and antimicrobial agents are in development as safe alternatives to preserve food products.<ref name=altay/>

===Battery electrolyte===
Chitosan is being investigated as an [[electrolyte]] for [[rechargeable batteries]] with good performance and low [[environmental impact]] due to rapid [[biodegradability]], leaving [[Recycling|recycleable]] zinc. The electrolyte has excellent physical stability up to 50&nbsp;°C, electrochemical stability up to 2&nbsp;V with zinc electrodes, and accommodates [[redox reaction]]s involved in the Zn-MnO<sub>2</sub> alkaline system. {{As of|2022}} results were promising, but the battery needed testing on a larger scale and under actual use conditions.<ref>{{cite journal | last1=Poosapati | first1=Aswani | last2=Vadnala | first2=Sudharshan | last3=Negrete | first3=Karla | last4=Lan | first4=Yucheng | last5=Hutchison | first5=John | last6=Zupan | first6=Mark | last7=Madan | first7=Deepa | title=Rechargeable Zinc-Electrolytic Manganese Dioxide (EMD) Battery with a Flexible Chitosan-Alkaline Electrolyte | journal=ACS Applied Energy Materials | publisher=American Chemical Society (ACS) | volume=4 | issue=4 | date=15 April 2021 | issn=2574-0962 | doi=10.1021/acsaem.1c00675 | pages=4248–4258| bibcode=2021ACSAE...4.4248P | s2cid=234870771 | hdl=11603/31329 | hdl-access=free }}</ref><ref>{{cite journal | last1=Poosapati | first1=Aswani | last2=Negrete | first2=Karla | last3=Thorpe | first3=Micah | last4=Hutchison | first4=John | last5=Zupan | first5=Mark | last6=Lan | first6=Yucheng | last7=Madan | first7=Deepa | title=Safe and flexible chitosan-based polymer gel as an electrolyte for use in zinc-alkaline based chemistries | journal=Journal of Applied Polymer Science | publisher=Wiley | volume=138 | issue=33 | date=6 April 2021 | issn=0021-8995 | doi=10.1002/app.50813 | article-number=50813| s2cid=233563261 | hdl=11603/31330 | hdl-access=free }}</ref><ref>{{cite news| last=Quaglia | first=Sofia | title=Crab and lobster shells could be used to make renewable batteries | newspaper=the Guardian | date=1 September 2022 | url=https://www.theguardian.com/science/2022/sep/01/crab-lobster-shells-could-used-make-renewable-batteries}}</ref>

==References==
{{reflist}}

==External links==
* International research project [https://archive.today/20150111074940/http://www.nano3bio.eu/ Nano3Bio], focused on tailor-made biotechnological production of chitosans (funded by the European Union)

{{carbohydrates}}
{{Authority control}}

[[Category:Antihemorrhagics]]
[[Category:Biopesticides]]
[[Category:Elicitors]]
[[Category:Polysaccharides]]